Novel NR5A1 missense mutation in premature ovarian failure: detection in han chinese indicates causation in different ethnic groups

PLoS One. 2013 Sep 20;8(9):e74759. doi: 10.1371/journal.pone.0074759. eCollection 2013.


Background: The etiology of most premature ovarian failure (POF) cases is usually elusive. Although genetic causes clearly exist and a likely susceptible region of 8q22.3 has been discovered, no predominant explanation exists for POF. More recently, evidences have indicated that mutations in NR5A1 gene could be causative for POF. We therefore screened for mutations in the NR5A1 gene in a large cohort of Chinese women with non-syndromic POF.

Methods: Mutation screening of NR5A1 gene was performed in 400 Han Chinese women with well-defined 46,XX idiopathic non-syndromic POF and 400 controls. Subsequently, functional characterization of the novel mutation identified was evaluated in vitro.

Results: A novel heterozygous missense mutation [c.13T>G (p.Tyr5Asp)] in NR5A1 was identified in 1 of 384 patients (0.26%). This mutation impaired transcriptional activation on Amh, Inhibin-a, Cyp11a1 and Cyp19a1 gene, as shown by transactivation assays. However, no dominant negative effect was observed, nor was there impact on protein expression and nuclear localization.

Conclusions: This novel mutation p.Tyr5Asp, in a novel non-domain region, is presumed to result in haploinsufficiency. Irrespectively, perturbation in NR5A1 is not a common explanation for POF in Chinese.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Asian Continental Ancestry Group / genetics*
  • Case-Control Studies
  • Causality
  • Ethnic Groups / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Molecular Sequence Data
  • Mutation, Missense / genetics*
  • Phenotype
  • Primary Ovarian Insufficiency / genetics*
  • Sequence Homology, Amino Acid
  • Steroidogenic Factor 1 / genetics*


  • NR5A1 protein, human
  • Steroidogenic Factor 1

Grant support

This work was supported by the National Basic Research Program of China [973 program-2012CB944700]; the National Natural Science Foundation of China [81000236,81270662]; Foundation for the Author of National Excellent Doctoral Dissertation of PR China (201078); and Independent Innovation Foundation of Shandong University, IIFSDU (2012TS130). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.